Biomedical subjects

N V Jiménez-Torres

Publications and source records attributed to N V Jiménez-Torres.

7 recordsLinked to original sources

PubMed2006

Population pharmacokinetic parameters of vancomycin in critically ill patients.

BACKGROUND: Intensive care unit patients are a highly heterogeneous population. Accurate dosing for this population requires characterization of the appropriate pharmacokinetic parameters. OBJECTIVE: To estimate population pharmacokinetic parameters of vancomycin (VAN) in adult critically ill patients and to establish the predictive performance of the resulting model. PATIENTS AND METHOD: Fifty critically ill patients with suspected or documented infection with VAN-sensitive micro-organisms were included. Thirty patients and 234 serum concentration-time sets obtained during clinical routine monitoring were used to estimate the pharmacokinetic parameters (group A). An open bicompartimental model with intermittent intravenous administration was used to adjust the data. Data were evaluated using a nonlinear mixed effects model (nonmem software). Forty plasma concentration-time data sets from 20 patients were used for validation using the Bayesian method (group B). RESULTS: There was a linear relationship between creatinine clearance (Cl(cr)) and VAN clearance (Cl(VAN)). The inclusion of the non-renal clearance (Cl(nr)) (intercept of Cl(VAN) vs. Cl(cr) relationship) improved the model significantly (Cl(nr) 17 mL/min). The volume of distribution seems to be larger than previously reported: volume of the central compartment (V(c)) was 0.41 L/kg and volume of the peripheral compartment was (V(p)), 1.32 L/kg. The mean error (bias) and mean absolute error (precision) for predicting subsequent peak concentrations were -2.16 and 9.28 mg/L and for trough concentrations, -0.22 and 3.87 mg/L respectively. CONCLUSION: The use of population-specific pharmacokinetic parameters and Bayesian forecasting improves dosage-regimen design.

Adolescent↗

PubMed2004

Adsorption of methotrexate and calcium leucovorin onto cholestyramine in vitro.

Methotrexate (MTX), an antimetabolite of folic acid, is a drug widely used in the treatment of different types of cancer. When high doses are administered, it is necessary to interrupt its action by administering calcium leucovorin (CaL). The main pathway of MTX and CaL elimination in humans occurs through the kidney, but about 10% is excreted in the faeces via the bile. Drugs, foods and sorbents in intestinal lumen modify MTX and CaL reabsorption. Individual and simultaneous studies on the adsorption of MTX and CaL from aqueous phosphate buffer by cholestyramine were carried out in order to calculate the adsorption process of MTX and CaL to cholestyramine, and to characterize the influence of CaL in the adsorption of MTX to cholestyramine and vice versa. The Langmuir binding isotherms determined in buffer solutions at pH 6 indicated a greater (12.58%) adsorption capacity of cholestyramine (1.43 mmol of drug/g of resin) than at pH 7 (1.25 mmol of drug/g of cholestyramine). The affinity constant of MTX to cholestyramine was a 45.27% higher (6.67 mM(-1)) than the affinity constant of CaL to the resin (3.65 mM(-1)). Results from simultaneous assays indicate that a displacement of the MTX bound to cholestyramine by CaL is not foreseeable. The results suggest that cholestyramine may be a potentially useful adjunctive therapy in the treatment of an overdose of MTX. Consequently, cholestyramine may be of clinical value in patients who develop early renal function impairment whilst undergoing MTX therapy.

Adsorption↗

PubMed2004

Relevance of multidrug resistance proteins on the clinical efficacy of cancer therapy.

Variations in drug uptake and efflux, as well as changes in intracellular drug entrapment and distribution may represent important resistance mechanisms to cancer therapy. A variety of ATP binding cassette transporters (ABC) localised in multiple cell membranes is implied in those phenomena, representing a mechanism of protection of cells against xenobiotics. Many cancer cell lines over express some ABC transporters, especially p-glycoprotein, MRP1 and BCRP. This over expression is related to worse cancer treatment outcome and, in some cases, reduced overall survival of cancer patients. This paper reviews the location and physiological role of the three transporters mentioned and also describes the drugs that are substrates of these proteins. The usefulness of animal and cellular models to evaluate the role of these transporters on the uptake and efflux of anticancer drugs is discussed. Finally, the results of preclinical and clinical studies about the utility of some inhibitors of these pumps, as well as the implications of polymorphism of ABC transporters on the efficacy and safety of anticancer therapeutics are reported.

Animals↗

PubMed2003

A Bayesian method for predicting 5-fluorouracil pharmacokinetic parameters following short-term infusion in patients with colorectal cancer.

The objective of this study was to develop a population pharmacokinetic model and validate it using a Bayesian approach for predicting, a priori and a posteriori, the individual volume of distribution (V(d)) and clearance (Cl) of 5-fluorouracil (5-FU) given as short-term intravenous infusion in weekly and multiple doses. Forty-four patients were divided in group A (5-FU weekly doses) including 27 patients with nonmetastatic colorectal adenocarcinoma treated with 450 mg/m(2) of 5-FU, 1 day per week for 48 doses, plus oral levamisol (50 mg/8 h) for 3 days, every 15 days and group B (5-FU multiple doses) including 17 patients with metastatic colorectal adenocarcinoma, receiving 5-FU (425 mg/m(2)) plus intravenous folinic acid (20 mg/m(2)) over 5 consecutive days, every 4 weeks for six cycles. In both groups 5-FU was administered as a 30-60-min infusion. A total of 176 plasma concentrations were analyzed using a NONMEM program according to a linear one-compartment model. In group A, 5-FU population pharmacokinetic parameters were obtained and the covariables studied were age, gender, weight, ideal body weight, height, body surface area, creatinine clearance, and hepatic function tests. A priori and a posteriori validation of this model was carried out with plasma concentrations obtained in day 1 in group B. In group B, population pharmacokinetic parameters of 5-FU following multiple doses were estimated using scale factors to identify differences in 5-FU V(d) and Cl between days 1 and 4, and the interindividual, interoccasion, and residual variabilities studied. V(d) was 0.266 L/kg of ideal body weight and Cl was 1.21 L/h. kg of total weight following weekly doses. The plasma sample obtained at 10 min gave the best accuracy and precision predictions. When 5-FU was administered in multiple doses, the Cl of the drug in day 4 is reduced by 30.14% compared to day 1. The interoccasion variability was lower than interindividual variability for both V(d) and Cl, suggesting that it could be feasible to individualise dosage of 5-FU for subsequent cycles from data obtained in a previous one in an attempt to improve the therapeutic index of colorectal cancer treatment.

Adult↗

PubMedDate not supplied

[Identifying improvement opportunities in the management of hepatitis C].

OBJECTIVE: Hepatitis C represents a public health concern with more than 170 million carriers. The goal of this study was to identify improvement opportunities in the management of hepatitis C, and the pharmaceutical actions performed for the prevention and solution of medication-related problems in patients seen at the Pharmaceutical Care Outpatient Unit. METHOD: A longitudinal study (January to October 2005) with patients monoinfected by hepatitis C virus receiving ribavirin and peginterferon alfa (2a or 2b). Data collection took place during the interview at the time of antiviral dispensation. Adverse reactions were classified according to CTCEA v3.0 criteria. Iaser methodology was used to identify patients with improvement opportunities regarding treatment. RESULTS: In all 109 patients and 201 improvement opportunities were identified. Pharmacotherapeutic morbidity was identified from adverse events (blood toxicity, pseudoflu syndrome, etc.) in 425 occasions; 388 pharmaceutical actions were performed, 41.23% to prevent adverse effects and 39.95% to provide patients or carers with information. CONCLUSIONS: In all, 99.01% of patients had safety problems. Pharmacotherapeutic morbidity from adverse effects was less common than reported in clinical trials of these drugs. Most pharmaceutical actions were preventive in nature. Iaser methodology allows to identify patients with improvement opportunities regarding hepatitis C treatment and the prevention of pharmacotherapeutic morbidity.

Adult↗

PubMedDate not supplied

High-dose methotrexate-doxycycline interaction.

OBJECTIVE: To report a case in which an interaction occurred between doxycycline and high-dose methotrexate (HD-MTX) and discuss its clinical, quality of life, and economic repercussions. CASE SUMMARY: A 17-year-old girl diagnosed with high-degree osteosarcoma in her left femur was admitted to our hospital to receive her eleventh postoperative cycle of HD-MTX, according to the clinical protocol approved at our hospital. Simultaneously, due to a palpebral abscess in her left eye, the patient received systemic treatment with doxycycline 100 mg every 12 hours. As in previous cycles, pharmacokinetic monitoring of methotrexate (MTX) plasma concentrations was performed to improve leucovorin calcium rescue. The biological half-life 12 and 24 hours after infusion showed that the patient was at high risk of intoxication. She then developed hematologic as well as gastrointestinal toxicity and remained hospitalized for 11 days. The patient was readmitted 48 hours after hospital discharge because of a febrile episode that required an additional hospital stay of 12 days, and the twelfth cycle of HD-MTX had to be postponed 18 days because of the results of the previous cycle. DISCUSSION: Significant differences (p < 0.05) were observed in the eleventh HD-MTX cycle for plasma concentrations and pharmacokinetic parameters compared with the previous 10 cycles. The interaction resulted in clinical, quality of life, and economic repercussions. CONCLUSIONS: The potential interaction between MTX and doxycycline may cause pharmacokinetic changes, and its clinical repercussions on the quality of life of the patient and associated costs should be considered.

Adolescent↗

PubMedDate not supplied

[Somatostatin stability in parenteral nutrition units].

The incorporation of somatostatin into parenteral nutritional units has considerable advantages in the treatment of patients subjected to this combined therapy with respect to a reduction in the cost of the therapy and an increase in its effectiveness. This study evaluates the stability of somatostatin in "all-in-one" parenteral nutritional units formulated with or without lipids and preserved at 5 or 25 degrees C for a study period of 7 days. The concentration of somatostatin was determined by high resolution liquid chromatography. All the parenteral nutritional units tested remained stable with regard to content in somatostatin for at least 7 days. The t90 values were around 13.3 days for nutritional mixtures without lipids preserved at 5 degrees C, manifesting the positive influence of refrigeration and lipid emulsion on the stability of somatostatin. None of the PNV showed modifications in pH, colour, precipitation or breakage of lipid emulsion during the study period. The above means that somatostatin can be prepared and administered together with Total Parenteral Nutrition in parenteral nutritional units formulated in the same container.

Drug Stability↗